RiteMED Cefalexin Mechanism of Action

Pharmacology: Pharmacodynamics: Cefalexin is a semi-synthetic, first generation cephalosporin which exerts its bactericidal activity by interfering with the bacterial cell wall synthesis. It binds to specific penicillin-binding proteins responsible for the synthesis of peptidoglycan, a heteropolymeric structure that gives the cell wall its mechanical stability. The final stage of peptidoglycan synthesis involves completion of the cross-linking of the terminal glycine residue of the pentaglycine bridge to the fourth residue of the pentapeptide. The transpeptidase enzyme that catalyzes this step is inhibited by cephalosporins. As a result the bacterial cell wall is weakened, the cell swells and then ruptures.
Pharmacokinetics: Cefalexin is acid stable and is rapidly and completely absorbed from the gastrointestinal (GI) tract. After single oral doses of cefalexin 250 mg and 500 mg in healthy, fasting adults with normal renal function, the mean peak serum concentrations (C_max) are 9 and 18 mcg/mL, respectively, and are achieved within one hour of administration. Serum concentrations are still detectable after 6 hours.
When cefalexin is administered with food, the peak serum concentrations are slightly lower and are attained later, although the total amount of drug absorbed remains unchanged.
Absorption of cefalexin is delayed in young children and may be decreased up to 50% in neonates. Peak serum concentrations of the drug have been reported to occur within 3 hours in infants younger than 6 months old, within 2 hours in children 9-12 months old, and within 1 hour in older children.
Cefalexin readily diffuses into tissues, including bone, joints and the pericardial as well as pleural cavities. It reaches therapeutic levels in the blood, urine, bile, synovial fluid, pus, tonsillar tissue, amniotic fluid, cord blood, and fetal blood. Cefalexin does not enter the cerebrospinal fluid (CSF) in significant quantities. The drug crosses the placenta and small quantities are found in breast milk.
The serum half-life (t_½) of cefalexin is 0.5 to 1.2 hours in adults with normal renal function. In adults with creatinine clearances of 13.5, 9.2 and 4 mL/minute, the serum t_½ were 7.7, 10.8, and 13.9, respectively.
Cefalexin is not metabolized in the body. It is excreted unchanged in the urine by both glomerular filtration and tubular secretion. About 70-90% of a single oral dose of cefalexin 250 or 500 mg is excreted within 8-12 hours in adults with normal renal function. Peak urine concentrations average about 2 mg/mL and occur 2 hours after a single 500 mg oral dose of cefalexin.
Microbiology: Antimicrobial Spectrum of Activity: Cefalexin is active in vitro and in clinical infections against most strains of the following microorganisms: See Table 1.

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Cefalexin is inactive against methicillin-resistant staphylococci and most strains of enterococci (e.g., Enterococcus faecalis), Enterobacter spp., Morganella morganii, and Proteus vulgaris. It has no activity against Pseudomonas spp. or Acinetobacter calcoaceticus. Penicillin-resistant Streptococcus pneumoniae is usually cross-resistant to beta-lactam antibiotics.
It is suggested to carry out susceptibility tests.